Author: Patrick
Publication: Molecular structure and misfolding mechanism of expanded polyglutamine proteins.
In a new report in the journal Proceedings of the National Academy of Sciences of the USA (PNAS) we provide important new insights into the misfolding and aggregation behavior of the mutant protein that causes Huntington’s Disease (HD). First authors Dr Cody Hoop and Dr Hsiang-Kai (Kyle) Lin used advanced solid-state NMR spectroscopy to study the structure of fibrils formed by huntingtin exon1 and related polyglutamine proteins. These state-of-the-art experiments allow us to elucidate a new beta-hairpin-based structure for the polyglutamine fibril core. In addition, our results provide important new insights into the stochastic self-assembly mechanism of expanded polyglutamine. This protein misfolding mechanism is likely active not only in HD, but also in other CAG repeat expansion disorders. The newfound molecular understanding of these disease-causing processes may facilitate the rational design of aggregation-modulating treatments or drugs.
For more information, read the article at PNAS.
ENC NMR conference coming to Pittsburgh
This coming spring the Experimental NMR Conference (ENC) is returning to Pittsburgh. The ENC poster, including a list of invited speakers, is available here. To submit your abstract, go to this page by Jan 8th 2016 (which is the abstract deadline). The registration deadline is March 18th 2016.
Dates: April 10-15, 2016
Location: Wyndham Grand Pittsburgh Downtown
Program: ENC website
New ssNMR spectrometer update
The new NIH-funded 750MHz solid-state NMR instrument has now been delivered to the Department of Structural Biology NMR facility. It is currently being installed and configured.
NEW: Photos of the installation process are available in this online gallery.
This state-of-the-art instrument adds exciting new capabilities for advanced MAS ssNMR to the facility, such as the inclusion of new ‘very-fast’ MAS probes. The spectrometer will facilitate and enhance our ongoing studies of protein misfolding and aggregation in Huntington’s Disease, and studies of the protein-lipid interactions underlying cell death and neurodegeneration.
Biophysical Society meeting news!
Congratulations to Jennifer and Abhishek, for being selected for a talk and awarded travel grants for the coming Biophysical Society Meeting in San Diego! We look forward to seeing you there, and tell you more about our studies of protein deposition diseases and protein-lipid interactions.
Update: see also the press release by the Biophysical Society.
Publication: Solid-state NMR studies of the pro-apoptotic peroxidase-form of cytochrome c.
Congratulations to Abhishek and his co-authors!
The Biophysical Journal has accepted our paper on the structural and functional study of cardiolipin-bound cytochrome c, looking at its peroxidase activated membrane-bound state. Lipid oxidation by cytochrome c plays a critical role in mitochondrial apoptosis, and we examined the molecular underpinnings of this process using solid-state NMR spectroscopy and other tools.
For more information see the paper:
Mandal, A., Hoop, C.L., DeLucia, M., Kodali, R., Kagan, V., Ahn, J., Van der Wel, P.C.A.* (2015) Structural changes and pro-apoptotic peroxidase activity of cardiolipin-bound mitochondrial cytochrome c. Biophys. J. J. 109(9): 1873–1884 (Full text)